TrustTheEvidence.net

Childhood obesity is bad news for heart disease in the future

Carl Heneghan — Wed, 26 Sep 2012 13:38:27 +0000

Apart from stating the obvious, we are in big trouble. Health services costs are rising and we can’t afford it. There are no new drugs to counteract the growing increase in chronic disease which cost us a fortune. Yet, to counteract all this we are getting fatter and fatter, and presenting a future steeped with dire consequences for our children.

Results from 63 studies of 49,220 children aged 5 to 16, published in today’s BMJ by our group, starkly illustrates the effect obesity has upon increasing risk of cardiovascular disease for future generations of children. We know that being overweight in adulthood increase your risk of heart disease and stroke, we now know that for children, these very same risk factors are increased markedly at a very young age.

Obese children have a blood pressure greater by 7.5mmHg than normal weight children. This rises to 11.5 mmHg when the more accurate ambulatory blood pressure readings are used. The increase seems to be greater for girls than boys: but the reason for this additional increase is unknown. Also, other important risk factors for heart disease are raised in obese children: blood lipids (cholesterol and triglycerides) are raised; fasting insulin and insulin resistance are worse and the left ventricular mass of the heart is increased when compared to normal children.

Being overweight as a child corresponds to a Body Mass index (BMI) of 25 to 30 and obesity as a BMI of over 30. BMI is a number calculated from a child's weight and height, and is weight in kg divided by height in metres squared (kg/m2). Although BMI does not measure body fat directly, it correlates with accurate measures of body fat, such as underwater weighing, and can be used as a simple measure for screening children.

Many countries use reference points in children to classify obesity, taking into account age, sex and a reference population. Whilst this data calculates an average for the population, and classifies obesity according to the degree of variation from this mean it may mask worrying trends due to increasing average weight of children over time. In 2007, the US obesity rates have nearly quintupled among 6- to 11-year-olds since the 1970s. Worryingly, in the UK school year, 2010/11, one third of children aged 10 to 11 were overweight or obese.

Like climate change, we know the problem is coming, but because the effects are at some point in the future, we are burying our heads in the sand, hoping the problem might just go away. For what is an easy situation to prevent: we need concerted action now. Jamie Oliver, once said "we're losing the war against obesity," We may have already lost it: 1 in 3 adults and 1 in 6 children are currently obese.

The importance of abstracts and press releases: the issue of "spin"

Peter Gill — Tue, 18 Sep 2012 23:12:45 +0000

Let’s be honest. Most researchers and clinicians only read the abstracts of research studies. This is true even when they diligently search out and find the original article that inspired a news headline. A cynical colleague suggested that people only read the Tweets of someone that only read the abstract of the article. People are busy and pressed for time; skimming abstracts is an efficient way to stay up-to-date with research findings without onerously sifting through pages of details. People want the bottom line. But this approach inherently relies on journals to ensure accuracy in abstract reporting.

Well, it seems this strategy is problematic for many reasons, particularly because of “spin” or “specific reporting emphasizing the beneficial effect of the experimental treatment.” A recent study in PLoS Medicine sought to quantify this problem: the authors identified two-arm, parallel-group RCTs, searched for associated press releases, and examined both for the presence of “spin.”

What they found was concerning: 47% of press releases and 40% of abstracts contained “spin.” After completing a multivariable analysis, “spin” in the article abstract was the only factor associated with “spin” in the press release (RR, 5.6; CI, 2.8-11.0; P<0.001). Therefore, the major driver of inaccurately reported findings was written by the author. In fact, 31% of press releases misinterpreted the results from the trial, either over- (86%) or under- (14%) estimating the benefit of the therapy.

Press releases are an important part of research dissemination. A study completed earlier this year in the BMJ by Evidence Live Faculty Lisa Schwartz and Steve Woloshin found that high quality press releases by journals can influence media coverage of the associated article. Increased coverage is beneficial if the press release is accurate which relies heavily on the abstract.

People involved in conducting research understand the importance of the abstract. This is the first piece read by a journal editor once submitted, and the decision to peer review largely relies on the authors ability to ‘sell’ their study in 300 words or less. Therefore, there is an incentive for authors to (over) emphasize the main results of the study in a manner that is usually critiqued in the peer review phase. While changes may be made to the full-text article to “dumb down” the authors conclusions, it is unclear how much the abstract changes as a result of peer review.

Realistically, the previously described process is unlikely to change, and everyone is not going to start reading the full-text article, particularly the media. Therefore, the onus is on journals to take an active role to ensure accuracy in abstract reporting and press releases. If they don’t, who will? If you want to learn more about what journals are doing to tackle this problem, come and ask the editors yourself at Evidence Live 2013.

*Note: this blog has also been posted on Evidence Live Blog.

Why bringing home the bacon isn't always the best thing

Kamal Mahtani — Thu, 13 Sep 2012 17:56:57 +0000

We consume too much salt. The problem is that high salt levels are associated with increased blood pressure and therefore increased risk of heart disease and stroke. Although the government says we should be consuming no more than 6 grams per day, we probably consume about 9 grams per day. The majority of that salt comes from processed foods rather than from adding salt at the table. Now a new survey from the UK based "Consensus Action on Salt & Health" (CASH) reveals what most lovers of a bacon sandwich probably don’t want to hear. Bacon has superseded ready meals, as the second highest contributor to salt in our diet with, in some cases, just 2 rashers providing half the total recommended daily amount. The survey reviewed the salt content of over 120 bacon packs available from high street supermarkets and found wide variations in bacon salt levels within the same supermarket. For example the supermarket Morrisons sells a Savers Smoked Rindless Back Bacon product with 6.8g salt per 100g bacon while also selling a different own brand pack with 2g salt per 100g. The CASH website has posted an industry response from Morrisons reporting that the supermarket will be targeting lower salt bacon products in the New Year.

So if bacon is the second highest contributor to salt, what is the first? I’m afraid it’s the bread holding your bacon sandwich together. Pre-packed bread and rolls remains the number 1 contributor to salt in the UK diet. The rest of the list includes fat spreads, cheese, sausages, cereals, ham and morning goods.

Hmmm….I think I’ll stick to my porridge for breakfast from now on.

The need to deliver ethical placebos

Dr Placebo — Tue, 31 Jul 2012 15:26:29 +0000

Clinical practice demands doctors provide the best available care. Some patients have non-specific complaints and there is no proven ‘active’ treatment. Placebos might benefit these patients. In other cases such as relieving pain placebos are known to have beneficial effects, while ‘active’ treatments have known side-effects. A problem is regulations all but forbid placebo use. But this is perverse – why would regulations prevent doctors from helping their patients?

Fortunately there other solutions. The reason placebos are considered unethical is they supposedly involve lying to patients. For example a doctors might tell their patient “this is a real treatment” when in fact it is a sugar pill. However placebos have been known to have effects even when doctors tell patients they are mere placebos. Hence doctors could simply inform patients that the treatment they prescribe is a placebo, and avoid the ethical problem. However it is likely that telling a patient that a treatment is a ‘placebo’ will reduce its effect.

But some patients may not care whether the treatment they are going to receive is a ‘placebo’, especially if such knowledge might reduce the benefit. These patients will undoubtedly want to know the treatment is safe, but have no interest in the ingredients or the label we place on the treatment. So, doctors could ask patients how much information they wish to receive about the treatment. The doctor could say, "Good morning Mrs Jones, my name is Dr Smith. This treatment has helped people with symptoms like yours, and it is known to be safe. We don't know exactly how it works, although some studies suggest it induces the body to produce various chemicals that can have benefits. Some patients like to know a lot about the treatments they use, while others don’t care and are willing to try and judge for themselves. If you would like to know more about the treatment I’m going to depend on you to prompt me. Does that seem like an acceptable way of proceeding?” Then, if the patients prefer to know more, the doctor might say that the treatment is sometimes referred to as a ‘placebo’, and add that much confusion surrounds the term. Or, if the patient doesn’t care, the doctor could refrain from revealing any further information.

This situation is familiar to us. Some Olympic athletes may wish to know everything about their opponents and the conditions, while others will find such information distracting.

As a patient, the amount of information you wish to receive about your treatments must be taken into account. Sometimes you will want to know everything, and at other times you may merely wish to know your treatment is safe.

Evidence-based mythbusting - a foray in sports products

Peter Gill — Mon, 30 Jul 2012 07:43:11 +0000

Myths are everywhere. Haunted forests. Greek Gods. You name it and there’s probably a myth for it. But what about myths related to sports? Surely athletes and consumers would not spend millions of dollars per year purchasing sports drinks, protein shakes and energy drinks if they didn’t work?

As outlined in the previous blog post on sports performance products, the CEBM team in Oxford looked at the evidence behind sports products. While completing the systematic assessment of the evidence underpinning claims six claims continually re-emerged.

Rather than use our traditional skills of evidence-based medicine, we experimented with a foray in evidence-based mythbusting (EBMythbusting).

Did your coach ever tell you to drink more fluid if the colour of your urine was dark? If they did, they better have provided you with a “urine colour chart” as athletes are less reliable than trained investigators at distinguishing the colour of their urine. Well if not, consider yourself lucky by having avoided many unnecessary trips to the toilet. The evidence is scarce to suggest that using urine colour is a useful or accurate as a marker of hydration. Best-case scenario is that first morning urine can tell you your hydration status.

Despite sport companies wanting you to believe that “Your brain may know a lot, but it doesn’t know when your body is thirsty. You need to drink during exercise before you feel thirsty in order to get enough fluids in your body to maintain your performance level”, the evidence suggests that drinking before you are thirsty may worsen performance and puts athletes at risk of hyponatraemia (low blood sodium levels). Apparently the human body worked before sports drinks were invented.

Does Red Bull really give you wings? Well the company at least states that “in extensive studies it has been repeatedly proven that Red Bull increases performance”. In reality any caffeine slightly improves performance (not flying), but is this surprising? Why else do we drink coffee in the morning?

Surely if protein and carbohydrate combinations after working out stimulates “increased uptake of glucose by the cells, resulting in faster glycogen storage” then it must improve performance. Unfortunately EBMythbusting has revealed that the effect is inconsistent and probably no better than a well-balanced and nutritious diet. Apparently Mom was right all along.

Pure branch chain amino acids. These just sound like they must work. Apparently they, amongst other things, can “help to sustain a healthy immune system during periods of intense training and play an important role in fatigue and performance”. Maybe, at best, and only to potentially reduce muscle soreness. But isn’t feeling sore after the gym a reminder that you exercised!

Sick of your skin? Do you want a second skin? Well here is the answer for you: “this ultra-tight, second-skin fit delivers a locked-in feel that keeps your muscles fresh and your recovery time fast”. Might as well stick to a massage or hot/icy cold-water therapy as these tend to work just as well to improve recovery.

EBMythbusting has challenged these common sports myths. Maybe practicing evidence-based medicine is really just an exercise in mythbusting. Why don’t you give it a try?

*Note: this blog has also been posted on Evidence Live Blog.

What's wrong with ordering a few reprints? New issues in publication bias

Peter Gill — Fri, 13 Jul 2012 17:09:36 +0000

A recent article published in the BMJ raises questions about the extent and type of publication bias that exists in the literature. Publication bias is the selected publication of studies based on the results, such as only publishing studies that demonstrate a drug works while not publishing studies that demonstrate harms.

The study authors, including Ben Goldacre author of the best-seller Bad Science, explore the potential implications of study funding and high reprint orders. They contacted the editors of the top general medical journals (i.e. JAMA, Lancet, NEJM, Ann Intern Med, and BMJ) and requested information on the 20 articles with the highest number of reprint orders. After matching the articles with controls, the authors evaluated whether study funding (i.e. industry, mixed, other or none) was associated with higher numbers of reprints.

The results are telling. The Lancet led the way with a median of 126,350 reprints for the top articles with a range from 24,000 to 835,100. The BMJ was a distant second with a median of 13,248 (range 1,000 to 526,650). Unfortunately JAMA, NEJM and Ann Intern Med did not provide information.

Overall, compared with controls papers with high reprint orders were considerably more likely to be funded by the pharmaceutical industry (odds ratio 8.64, 95% CI 5.09 to 14.68). In addition the cost for reprint orders ranged from £4,002 to £1,551,794: reprints are evidently a lucrative source of supplementary income for journals.

While not designed to detect publication bias, the article highlights the importance of thinking outside the box. Evidence-based medicine is filled with cutting edge issues that are continually evolving and emerging. Do you think that a paper with potentially high reprint orders may affect an editor’s decision to publish? Should journals disclose the number of reprints for each article?

If you are keen to learn more, consider attending Evidence Live, a conference unlike any other event in healthcare, bringing together the leading speakers in evidence-based medicine from all over the world. The conference will include a session dedicated to Publication Bias at Evidence Live 2013 with an international line-up of speakers including Doug Altman, An-Wen Chan, Tom Jefferson and many more.

What do you think are undiscovered sources of publication bias? Here's your chance to share your thoughts with the experts at the University of Oxford, 25-26 March 2013.

*Note: this blog has also been posted on Evidence Live Blog.

South Asians, ethnicity and cardiovascular disease:no easier to unravel than genetics

Ami Banerjee — Mon, 25 Jun 2012 22:59:41 +0000

South Asians (people from India, Pakistan, Bangladesh, Nepal, Maldives and Sri Lanka) seem to have high rates of heart attacks and stroke (collectively known as cardiovascular disease) that is not explained by widely-known risk factors such as high blood pressure or smoking. When you consider that the Indian subcontinent accounts for over 1.4 billion people and carries the greatest global burden of cardiovascular disease, it is important to understand what puts these people at increased risk, even when they migrate to other countries.

I have spent this week at Northwestern University in Chicago, learning about their great programme of clinical research into the causes of cardiovascular disease. I heard of my favourite ever acronym for a study, “MASALA” (The Mediators of Atherosclerosis in South Asians Living in America) which is recruiting 1000 South Asians in Chicago and San Francisco and will compare risk factors and development of heart disease. Interestingly, whereas study of South Asians has been at the forefront of research regarding ethnicity and cardiovascular disease in the UK, study of ethnic disparities in health has tended to focus on African American populations.

It is well-known that risk of stroke and risk of heart disease are linked to socio-economic status. In a London-based study of 1400 South Asian men, deaths from heart attacks and stroke were more likely in men whose fathers had “manual” occupations, or in men who had completed less than 11 years of formal education. This effect was more marked in men who themselves were engaged in manual work, and the authors concluded that “childhood socioeconomic position”, together with adult socioeconomic position cumulatively influenced the risk of dying of from cardiovascular disease. Studies in Scotland have shown similar results. There is definitely a relationship with socioeconomic deprivation and heart disease in Indians living in India How do we best measure “social disadvantage”? Do we need a “social disadvantage index”, as has been proposed by Canadian researchers led by Salim Yusuf? They found that social disadvantage was higher among older people, women, and non-white ethnic groups. The jury is still out regarding the best way to measure socioeconomic status, but it does appear that ethnic minorities, including South Asians, tend to suffer from a greater degree of social deprivation, which may contribute to cardiovascular disease. However, results of the 2010 US census show that Indians living in America have higher income than other ethnic groups and are the fastest growing ethnic minority, so socioeconomic status is not telling the whole story about the high rates of cardiovascular disease in America.

What about migration? The Indian Migrant Study and other studies suggest that South Asians who migrate within their countries from rural to urban areas, as well as those who move to Western countries, seem to have increased risk of heart attack and stroke, and there seem to be roles for socioeconomic status, risk factors and migration itself.

In the UK, one study has shown higher reported “psychosocial adversity” in South Asians who had suffered heart attacks, compared with UK whites, in terms of greater chronic stress, in the form of financial strain, residential crowding, family conflict, social deprivation and discrimination, despite larger social networks. These effects were largely independent of socioeconomic status. Linguistic and cultural barriers have been previously cited as potential causes of higher rates of heart attacks in South Asians, but it is not as simple as that, as Hindus and Sikhs were more likely to seek help for chest pain than their white European counterparts in one study.

Lifestyle is also likely to be very important and many differences seem to manifest in early childhood, such as lower physical activity in South Asians and higher saturated fat intake in Indians.
Last year, I wrote about research looking at ethnicity and risk of stroke in the UK and the USA. As I said then, the research continues to describe differences in traditional and non-traditional risk factors, but not so much has been done to design and implement interventions to reduce the variations in health due to ethnicity. The interplay of environmental factors and ethnicity in cardiovascular disease is no less complex than the interplay of genes and environment. Encouragingly, the discourse about the best policies to tackle health disparities related to ethnicity is well underway on both sides of the pond.

Publication bias: big problem for children

Peter Gill — Sun, 06 May 2012 15:44:38 +0000

A recent study in the journal Pediatrics reported that only 29% of clinical studies in children have been published. This finding reinforces previous studies that there is significant publication bias in paediatric studies. These findings are a cause for serious concern.

What is publication bias? Essentially, it is the selected publication of studies based on the results, such as only publishing studies that demonstrate a drug works while not publishing studies that demonstrate harms.

Publication bias is a serious problem in healthcare and can have a large influence on treatment decisions by only providing limited information. Researchers have demonstrated substantial publication bias in certain areas such as the antidepressant medication reboxetine.

Several initiatives have been spearheaded to help reduce publication bias. The creation of open-access journals have shifted the focus from the importance of the results (as judged by a journal editorial committee) to the methodological rigour by which the study was completed.

But more importantly has been the creation of online trial registries, such as ClinicalTrials.gov launched in 2000. These registries serve as central databases of all the current and on-going clinical studies. Registration is optional, however in 2005 the ICMJE made registration of clinical trials as a pre-requisite of publication. Although this does not represent all journals, it sent a strong message of the importance of registration.

However despite the creation of trial registries, less than half of US based National Institute of Health (i.e. government) funded trials in children were registered on ClinicalTrials.gov. Another important finding was the lack of information included on the registries. One-third of all clinical studies terminated early did not provide any information about why they were stopped. The situation was similar for suspended studies with one quarter not providing information.

Were these studies stopped because of harms? Were the investigators no longer able to recruit children to enroll? Whatever the reason the studies were stopped, this information must be made public.

Registration of all clinical studies involving children must be made mandatory. This is the only way to minimise publication bias and increase the reporting of research. This would create massive industry uproar, but is it ethical to enroll children in a clinical study without having it publicly registered? At a minimum any trial that receives government funded must be registered.

However registration of studies is only one element of the formula. What about the dissemination of the results? Less than 10% of completed studies in children had results posted and publicly available. With the low publication rates of registered studies, and the even lower rate of posting results, how much information is still missing?

Indeed progress has been made to increase the quality and transparency of clinical studies in children but more is needed. We cannot assume that because trial registries exist that they are being used. Complacency must be replaced with compliance. It seems that more often than not, the little ones have the biggest problems.

Increasing access to journals through peer reviewers

Peter Gill — Mon, 23 Apr 2012 08:00:19 +0000

A recent letter to the editor in the Canadian Medical Association Journal (CMAJ) highlighted a potential opportunity to increase access to subscription-based journals for individuals in low and middle-income countries. It turns out that a few journals give their peer reviewers’ free journal access or a free subscription as a thank you gift for their effort.

How widespread is this policy in the medical publishing world?

Unfortunately not very. Of the 21 journal editors contacted (including CMAJ, Lancet, BMJ, JAMA, etc.), only three actually provide reviewers with free journal access. The gift ranges from a 3-month (Lancet) to a 12-month subscription (BMJ and the Journal of Intellectual & Developmental Disability).

On the positive side, 20 out of the 21 journals were members of the Health InterNetwork Access to Research Initiative (HINARI), the World Health Organisation’s programme to provide free or low cost online access in the developing world to scientific research. This is encouraging, but HINARI is not perfect and many are still left without access.

For example, a BMJ Rapid Response highlighted that health care workers in middle-income countries such as Malaysia are often caught in the middle. Too rich for aid but not wealthy enough to afford the high cost of journal subscriptions.

However, despite the fact that most original research relevant to low and middle-income countries is open-access, the majority of the education articles, clinical reviews, news pieces and commentaries are still often behind firewalls that require payment.

The move for more open-access journals is encouraging. For example, the Howard Hughes Medical Institute, the Max Planck Society and the Wellcome Trust will be launching eLife, a new open access journal later this year.

Why don’t more journals provide peer reviewers with free subscriptions? Not only is it a symbol of appreciation for the hours of gratuitous time altruistically invested but it could be used to help others. Likely there is no pressure or demand for it. The majority of peer reviewers are already at academic institutions with subscriptions.

Has this happened to you before? What have you done with this free gift? Although few journals seem to be endorsing this policy, it may serve as a small way to increase access to those who otherwise do not have it.

In the future, if you review an article for the BMJ, the Lancet or the Journal of Intellectual & Developmental Disability (or other journals that provide free subscriptions after peer reviewing), rather than deleting the email consider who might benefit.

If you review for a journal that does not, ask the editor why not?

Aspirin and prevention-who knows best?

Ami Banerjee — Fri, 30 Mar 2012 16:09:28 +0000

As the UK descends into hysteria around petrol and pasties, I have been reflecting for the last week on Peter Rothwell’s recent Lancet papers about cancer prevention and the role of aspirin. Basically, daily low-dose aspirin not only prevents development of new cancer, but also the spread of cancer. Aspirin is one of the oldest drugs in the drug cabinet of hospital wards and GP surgeries, but we continue to discover more about its roles in medicine. As new evidence appears on the horizon, the information and guidelines for practising doctors and their patients still continues to change. There are inevitably time delays in how quickly new information filters through healthcare settings and broader society, and how it is interpreted by both the patient and the doctor.

Aspirin has several different uses which are proven by large bodies of evidence, including as a painkiller, prevention of cardiovascular disease in people at risk (primary prevention) and people with known cardiovascular disease (secondary prevention) and now for prevention of cancer. I always love to refer back to the Hippocratic Oath, and so we have to weigh aspirin’s harms with these many benefits. The main harm with aspirin is bleeding, particularly people who have a tendency towards bleeding anyway, e.g. individuals with history of gastric ulcers.

Interestingly, as the new data is emerging about the long-term preventive effects on cancer, the use of aspirin for two other indications is in decline due to evidence of not that much good when weighed against the risk of bleeding. First, most doctors do not recommend low-dose aspirin for primary prevention of cardiovascular disease, largely due to available data from meta-analyses showing that it does not change mortality in diabetics or non-diabetics. Second, in patients with atrial fibrillation, a heart rhythm problem which increases risk of stroke, aspirin is no longer recommended, yet most guidelinesaround the world still include it. So while we can recommend aspirin for long-term cancer prevention, we may not be able to recommend it in healthy individuals for long-term stroke prevention.

Evidence-based medicine is following a moving target of diseases and treatments and so the evidence is also always changing, even for drugs as old as aspirin. So for newer drugs, you can begin to imagine how little we know. The challenge is to keep all people, both doctors and patients up-to-date with all available evidence and guidelines. However, we know that this is difficult, given that both doctors do not always follow guidelines and people do not generally like to take tablets. Notably, most news reports covering the “aspirin and cancer” story advised people to go and see their doctor before starting the drug. Fergus Walsh, of the BBC, quoted a notable academic, “Doctors were good at treating disease, but when it came to preventing ill-health then people had to make their own judgements”. I agree. I wonder whether people have as much chance of making the “right decision” themselves. And before you ask, I do not take an aspirin a day yet, but I did start cycling to work again this week. One preventive step at a time.